Multiple sclerosis is a nervous demyelinating disease with unknown etiology which is clinically characterized in that recurrence and remission are repeated and often develops into progressive physical disability. It is known that multiple sclerosis causes visual impairment, loss of equilibrium sense, poorly coordinated movement, slurred speech, tremor, numbness, extreme fatigue, alteration of intellectual functions, muscular weakness, paresthesia, and blindness (see, for example, Non-patent Literature 1 and Non-patent Literature 2).
Although it is said that there are 2,500,000 patients suffering from multiple sclerosis in the world, there may be a lot of potential patients who are not diagnosed yet due to the difficulty to detect the symptoms. In addition, multiple sclerosis is a chronic disease which repeats recurrence and remission and QOL of the patients is often seriously disturbed. Therefore, the importance of therapy for multiple sclerosis is increasing year by year.
Multiple sclerosis cannot be cured and the therapy is performed mainly by means of symptomatic treatments. Such treatments alleviate or prevent the symptoms, but cannot cure demyelination which is the basic defect of this disease. Corticosteroids which shorten the period of recurrence are used in the present therapy. However, a long-term improvement effect on the course of the disease has not been observed. In some cases, immunosuppressants, cyclophosphamide, leflunomide and cyclosporin A are used for progressive multiple sclerosis. However, it is known that such agents have a teratogenicity and carcinogenicity.
Thus, the therapeutic agents for multiple sclerosis now existing are not fully satisfactory with respect to effects thereof and reduction of side effects.
On the other hand, Patent Literature 1 discloses a use of the compounds represented by the below-described Formula:
(wherein Ar represents substituted phenylene or the like, L represents —S(O)2— or the like, X represents a bond or the like, Z represents COOH or the like, R2, R3, R4 represent hydrogen or the like, R5 represents —C2-10 alkenyl-aryl-NRdRe-heteroaryl-(Rd, Re represent hydrogen, C1-10 alkyl) or the like, R6 represents hydrogen or the like), which can be considered to be structurally similar to the compounds contained as an effective ingredient in the present invention, for the therapy of multiple sclerosis. However, the compounds whose use mentioned above is disclosed in the publication are structurally different from the compounds in the present invention in that the disclosed compounds are characterized in that Ar in the Formula is substituted with aminoalkyl structure (R1LN(R2)CHR4—: R1 represents substituted aryl or the like). Moreover, concrete data which demonstrate the effectiveness against multiple sclerosis are not described, therefore the publication fails to fully disclose that the compounds really have the therapeutic effect. Activity thereof when orally administered is also not disclosed.
In claims of Patent Literatures 2 and 3, use of the compounds represented by the Formula:X—Y—Z-Aryl-A-B(wherein X represents a 6-membered aromatic ring comprising two nitrogen atoms or the like, Y represents —C0-6 alkylene-NC1-10 alkyl-C0-6 alkylene- or the like, Z represents a bond or the like, Aryl represents a 6-membered aromatic ring, A represents —(CH2)C═C(CH2)n—(n=0-6) or the like, B represents —CH (substituted aryl-carbonylamino)CO2H or the like), which includes the compounds in the present invention, as a bone resorption inhibitor and platelet aggregation inhibitor is described. However, the compounds in the present invention are not concretely described in the publications. The use disclosed therein is also totally different from that of in the present invention. The therapeutic or prophylactic effect on multiple sclerosis according to the present invention is not suggested at all.
Patent Literature 4, which was published after the priority date of the present application, discloses a compound which is contained as an effective ingredient in the present invention and use thereof for therapy of inflammatory bowel disease. However, the therapeutic or prophylactic effect on multiple sclerosis according to the present invention is not disclosed at all.    Patent Literature 1: WO 99/26923    Patent Literature 2: WO 95/32710    Patent Literature 3: WO 94/12181    Patent Literature 4: WO 2006/068213    Non-patent Literature 1: Proc. Soc. Exp. Biol. Med., 175, 282-294 (1984)    Non-patent Literature 2: Immunol. Rev., 100, 307-332 (1987)